The effect of aging on the biological and immunological characteristics of periodontal ligament stem cells

Li, Xiaoyu; Zhang, Bowen; Wang, Hong; Zhao, Xiaolu; Zhang, Zijie; Ding, Gang; Wei, Fulan

doi:10.21203/rs.3.rs-17276/v3

Cited by 7 publications

(8 citation statements)

References 44 publications

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“…FKBP1A is recognized as autophagy‐related gene, which is a target of drugs including Rapamycin and FK506 (Feng et al, 2021; Ghartey‐Kwansah et al, 2018; Liu et al, 2017). Some studies found that FKBP1A is involved in aging, apoptosis, and proliferation (Leng et al, 2020; Li et al, 2020; Seguinot‐Tarafa et al, 2020). Besides, FKBP1A is implicated in inflammation by complementary DNA (cDNA) array results and genomic network results (Saban et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Dendrobine modulates autophagy to alleviate ox‐LDL‐induced oxidative stress and senescence in HUVECs

Xing

Liang

2022

Drug Development Research

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Dendrobine has potential advantages in suppressing atherosclerosis (AS). FK506‐binding protein 1A (FKBP1A) is implicated in the regulation of autophagy, inflammation, and apoptosis. To reveal the mechanism by which dendrobine inhibits AS by modulating autophagy, oxidative stress, apoptosis, and senescence. An in vitro AS cell model was induced by culturing human umbilical vein endothelial cells (HUVECs) with oxidized low‐density lipoprotein (ox‐LDL). The cells were treated with dendrobine alone or in combination with short hairpin RNA (shRNA) targeting FKBP1A or together with 3‐methyladenine (3MA), an autophagy inhibitor. Inflammatory cytokines levels tumor necrosis factor‐α, interleukin‐6 (IL‐6), and IL‐1β were analyzed and oxidative stress levels were detected by the analysis of reactive oxygen species, malondialdehyde, and superoxide dismutase levels, followed by the analysis of apoptosis levels through terminal deoxynucleotidyl transferase dUTP nick end labeling staining. Cell senescence was evaluated by senescence‐associated β‐galactosidase and light chain 3 (LC3) levels were detected by immunofluorescence (IF) staining. The targeting relationship of dendrobine and FKBP1A was predicted by SwissTarget, PyMol, Autodock, and Open Babel software. Dendrobine reduced the levels of proinflammation factors, oxidative stress levels, apoptosis levels, and senescence phenotype in ox‐LDL‐induced HUVECs. Besides, cell viability has an opposite change. Furthermore, there was an increase in LC3 IF tensity, and LC3‐II/I and Beclin1 expressions, and a decrease in p62 expression. However, these effects of dendrobine could be markedly destroyed by shRNA silencing FKBP1A and 3MA. Dendrobine can suppress inflammatory responses, oxidative stress, apoptosis, and senescence via FKBP1A‐involved autophagy ox‐LDL‐treated HUVECs.

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Section: Introductionmentioning

confidence: 99%

Dendrobine modulates autophagy to alleviate ox‐LDL‐induced oxidative stress and senescence in HUVECs

Xing

Liang

2022

Drug Development Research

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“…The specific method of Western blot was described in our previous study. 26 Primary antibodies used include JNK (1:1000; CST), P-JNK (1:1000;…”

Section: Western Blot Analysismentioning

confidence: 99%

Periodontal ligament stem cells promote polarization of M2 macrophages

Liu

Wang

Zhang

et al. 2022

Journal of Leukocyte Biology

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Macrophages are widely distributed in a variety of tissues, and the different state of macrophages polarization is closely related to the occurrence, development, and prognosis of inflammation, including periodontitis, a chronic inflammatory disease leading to tooth loss worldwide. Periodontal ligament stem cells (PDLSCs) play a key role in immune regulation and periodontal tissues regeneration, contributing to cell-based therapy of periodontitis. However, the interactions between PDLSCs and macrophages are still elusive. The purpose of present study is to investigate the effect of PDLSCs conditioned medium (PDLSCs-CM) on the macrophage polarization and the possible mechanism. PDLSCs were isolated using tissue explant methods and characterized via multipotent differentiation test and examination of expression profiles of mesenchymal stem cells (MSCs) markers. The supernatant of PDLSCs was collected, centrifuged, filtered, and used as PDLSCs-CM. Then, PDLSCs-CM was cocultured with M0 macrophages or IL-4-and IL-13-induced M2 macrophages. The level of surface markers of M1/M2 macrophages and production of several proinflammatory or antiinflammatory factors were evaluated by flow cytometric analysis and enzyme-linked immunosorbent assay, respectively. The associated genes and proteins involved in the JNK pathway were investigated to explore the potential mechanism that may regulate PDLSCs-CM-mediated macrophage polarization. PDLSCs expressed MSCs markers, including STRO-1, CD146, CD90, and CD73, and were negative for CD34 and CD45, could undergo osteogenic and adipogenic differentiation when cultured in defined medium. After incubation with PDLSCs-CM, no significant increase of CD80+ and HLA-DR+ M1 macrophages was shown while evaluated CD209+ and CD206+ M2 macrophages were observed. In addition, the levels of anti-inflammatory factors such as IL-10, TGF-β, and CCL18 were increased instead of proinflammatory factors such as IL-1β, TNF-α with PDLSC-CM treatment. There was a decrease of JNK expression on M0 macrophages by qRT-PCR analysis and an increase of protein phosphorylation on M0 macrophages after incubation with PDLSCs-CM. Furthermore, as for the enhancement of IL-4-and IL-13-mediated M2 polarization by PDLSCs-CM, the mRNA level of

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“…A functional shortage in adult stem cells caused by cellular senescence may be regarded as a major driver of age-related deterioration in endogenous tissue healing and regenerative potential (Sharpless and DePinho 2007). Li et al (2020) illustrated the effects of age on periodontal ligament stem cells (PDLSCs) by comparing PDLSCs from young and elderly donors. They found that the proliferation, osteogenic/adipogenic/chondrogenic differentiation, and immunosuppressive ability of PDLSCs decreased, whereas apoptosis increased with the aging process.…”

Section: Molecular Hallmarks Of Aging In Periodontal Tissuesmentioning

confidence: 99%

Periodontitis and Accelerated Biological Aging: A Geroscience Approach

et al. 2021

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As the whole world is epidemically aging, the burden of periodontitis and tooth loss is becoming a major health concern. Growing meta-epidemiological data implicate chronic systemic inflammation/infection due to periodontitis as an independent risk factor for aging-related diseases and mortality. However, because people age differently, chronological age is not a reliable marker of an individual’s functional status. Recent advances in geroscience have shown that various biomarker signatures of biological aging are longitudinally associated with declined physical function, morbidity, and mortality due to major age-related diseases, including periodontitis. Here, we emphasize novel research developments bidirectionally linking periodontitis to accelerated biological aging. Using a composite biomarker age estimator, a striking increase in periodontitis and tooth loss was observed in subjects whose biological age at baseline was higher than their chronological age. Moreover, significantly shortened telomeres were encountered in populations affected by severe periodontitis. Second, we elucidate the cellular and molecular pillars of the aging process at the periodontal level. Accumulating evidence suggests that cellular senescence, stem cell exhaustion, and immunoaging are hallmarks of biological aging implicated in the impairment of periodontal homeostasis and the pathophysiology of periodontitis. Indeed, persistent bacteria-derived lipopolysaccharide stimulation influences cellular senescence in osteocytes, driving alveolar bone resorption. Moreover, inflammaging status induced by chronic hyperglycemia elevates the burden of senescent cells in gingival tissues, impairing their barrier function. Lastly, we reviewed a recent breakthrough in senotherapy to directly target the mechanisms of aging at the periodontal level. Physical exercise and intermittent fasting, together with natural compounds, senolytic drugs, and cell therapy, are increasingly being evaluated to rejuvenate the oral cavity. Following these innovations in geroscience, further advancements could provide oral clinicians the chance to intercept biological aging when still “subclinical” and set interventions for halting or delaying the trajectory toward aging-related diseases while patients are still chronologically young.

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The effect of aging on the biological and immunological characteristics of periodontal ligament stem cells

Cited by 7 publications

References 44 publications

Dendrobine modulates autophagy to alleviate ox‐LDL‐induced oxidative stress and senescence in HUVECs

Dendrobine modulates autophagy to alleviate ox‐LDL‐induced oxidative stress and senescence in HUVECs

Periodontal ligament stem cells promote polarization of M2 macrophages

Periodontitis and Accelerated Biological Aging: A Geroscience Approach

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